Neuronal nitric oxide synthase and calbindin delineate sex differences in the developing hypothalamus and preoptic area

Abstract

Throughout the hypothalamus there are several regions known to contain sex differences in specific cellular, neurochemical, or cell grouping characteristics. The current study examined the potential origin of sex differences in calbindin expression in the preoptic area and hypothalamus as related to sources of nitric oxide. Specific cell populations were defined by immunoreactive (ir) calbindin and neuronal nitric oxide synthase (nNOS) in the preoptic area/anterior hypothalamus (POA/AH), anteroventral periventricular nucleus (AVPv), and ventromedial nucleus of the hypothalamus (VMN). The POA/AH of adult mice was characterized by a striking sex difference in the distribution of cells with ir-calbindin. Examination of the POA/AH of androgen receptor deficient Tfm mice suggests that this pattern was in part androgen receptor dependent, since Tfm males had reduced ir-calbindin compared with wild-type males and more similar to wild-type females. At P0 ir-calbindin was more prevalent than in adulthood, with males having significantly more ir-calbindin and nNOS than have females. Cells that contained either ir-calbindin or ir-nNOS in the POA/AH were in adjacent cell groups, suggesting that NO derived from the enzymatic activity of nNOS may influence the development of ir-calbindin cells. In the region of AVPv, at P0, there was a sex difference with males having more ir-nNOS fibers than have females while ir-calbindin was not detected. In the VMN, at P0, ir-nNOS was greater in females than in males, with no significant difference in ir-calbindin. We suggest that NO as an effector molecule and calbindin as a molecular biomarker illuminate key aspects of sexual differentiation in the developing mouse brain.

Role of Nitric Oxide and Flavohemoglobin Homolog Genes in Aspergillus nidulans Sexual Development and Mycotoxin Production

“…NO has been shown to regulate multiple physiological processes, particularly in mammals (6,12,15,18,22,31). These reports reflect that one of the important roles of NO in higher eukaryotes is the regulation of reproduction in males and females.…”

Kisspeptin-GPR54 Signaling in Mouse NO-Synthesizing Neurons Participates in the Hypothalamic Control of Ovulation

“…Since NO cannot be stored in synaptic vesicles, unlike other neurotransmitters, mechanisms that regulate its synthesis in time and space are crucial in determining its biological effect (Garthwaite, 2008). In the mouse (Clasadonte et al, 2008;present study), as in the rat (Grossman et al, 1994;Herbison et al, 1996), GnRH neurons are surrounded by NO-synthesizing neurons in the basal forebrain, one of the major sites of NOS expression in the CNS (Bredt et al, 1991;Yamada et al, 1996;Edelmann et al, 2007). The production of neuronal NO in the vicinity of GnRH neurons is tightly regulated by estrogens (d 'Anglemont de Tassigny et al, 2007a;Parkash et al, 2010) and has been shown to directly modulate GnRH neuronal activity (Clasadonte et al, 2008).…”

Genetic dissection of neural circuits underlying sexually dimorphic social behaviours

“…As discussed above, these receptors can regulate gene expression, and many hormone-dependent sex differences in gene expression have been identified, including in the sex hormone receptors themselves and the enzyme aromatase that converts testosterone into 17b-oestradiol [10][11][12][13][14][15][16][17][18][36][37]40]. For example, we have used genetic strategies to visualize the expression pattern of aromatase in the brain and discovered that it is expressed in a few discrete areas, including the posterodorsal MeA (MeApd) and the posteromedial part of medial division of the BNST (BNSTmpm).…”